Neuron-glia interactions play a critical role in the maturation of neural circuits; however, little is known about pathways that mediate their communication developing CNS. We investigated neuron-glia signaling retina, where we demonstrate retinal waves reliably induce calcium transients Müller glial cells (MCs). During cholinergic waves, MC were blocked by muscarinic acetylcholine receptor antagonists, whereas during glutamatergic inhibited ionotropic glutamate indicating responsiveness MCs...

In healthy adults, activation of γ-aminobutyric acid (GABA) A and glycine receptors inhibits neurons as a result low intracellular chloride concentration ([Cl – ] i ), which is maintained by the potassium-chloride cotransporter KCC2. reduction KCC2 expression or function implicated in pathogenesis several neurological disorders, including spasticity chronic pain following spinal cord injury (SCI). Given critical role regulating strength robustness inhibition, identifying tools that may...

Bistability is not a common feature of all mouse spinal motoneurons. It absent in small, slow motoneurons but present most large, fast This difference results from differential expression ionic currents that enable bistability, which are highly expressed large small or These support possible role for maintenance tonic posture addition to their known roles movements.

Spinal motoneurons are endowed with nonlinear spiking behaviors manifested by a spike acceleration whose functional significance remains uncertain. Here, we show in rodent lumbar that these properties do not rely only on activation of dendritic nifedipine-sensitive L-type Ca2+ channels, as assumed for decades, but also the slow inactivation K+ current mediated Kv1.2 channels highly expressed axon initial segments. Specifically, pharmacological and computational inhibition occluded...

Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by brief excitation bistable motoneurons and bursting oscillations interneurons of central pattern generator (CPG). Here, we identify NaV channels responsible for INaP their role motor behaviors. We report axonal Nav1.6 as main molecular player lumbar motoneurons. The inhibition Nav1.6, but not Nav1.1, impairs INaP, bistability, postural tone,...

Abstract Spasticity, a prevalent motor issue characterized by network hyperexcitability, causes pain and discomfort, with existing treatments offering limited relief. While past research has focused on neuronal factors, the role of astrocytes in spasticity been overlooked. This study explores potential restoring astrocytic potassium (K+) uptake to reduce following spinal cord injury (SCI). Astrocytes buffer extracellular K+ via Kir4.1 channels, preventing hyperexcitability. Following SCI,...

A Ca2+-dependent transglutaminase (EC 2.3.2.13) has been demonstrated in the eye lenses of several mammalian species [Lorand, L., Hsu, L. K. M., Siefring, G. E., Jr., & Rafferty, N. S. (1981) Proc. Natl. Acad. Sci. USA 78, 1356-1360]. Using [3H]methylamine as a convenient probe for activity, we have explored action this enzyme bovine lens. We could characterize glutamine residues acting acyl-donor sites three beta-crystallin chains, which are only substrates lens among various...

Patterned, spontaneous activity plays a critical role in the development of neuronal networks. A robust is observed <i>in vitro</i> spinal cord preparations isolated from immature rats. The rhythmic ventral root discharges rely mainly on depolarizing/excitatory action GABA and glycine early during development, whereas at later stages glutamate drive primarily responsible for GABA/glycine are thought to play an inhibitory role. However, mediated by activation GABA_A receptors...

Abstract Neuronal rhythmogenesis in the spinal cord is correlated with variations extracellular K + levels ([K ] e ). Astrocytes play important role [K homeostasis and compute neuronal information. Yet it unclear how oscillations are regulated by astrocytic homeostasis. Here we identify inward‐rectifying channel Kir4.1 (a.k.a. Kcnj10 ) as a key molecular player for rhythmicity central pattern generator (CPG). By combining two‐photon calcium imaging electrophysiology, immunohistochemistry...

Abstract Bistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na + and triggered a brief excitation. The thermoregulating molecular mechanisms bistability their role in motor functions remain unknown. Here, we identify thermosensitive -permeable Trpm5 channels as main players for mouse motoneurons. Pharmacological, genetic or computational inhibition occlude bistable-related properties (slow afterdepolarization, windup, potentials) reduce locomotor...

The interaction of 125I-labelled tissue-type plasminogen activator (125I-t-PA) with freshly isolated rat parenchymal and endothelial liver cells was studied. Binding experiments at 4 degrees C indicated the presence 68,000 44,000 high-affinity t-PA-binding sites, an apparent Kd 3.5 nM respectively. Association 125I-t-PA Ca(2+)-dependent not influenced by asialofetuin, a known ligand for galactose receptor. mannose-specific, since ovalbumin (a mannose-terminated glycoprotein) inhibited cell...

The bleeding syndrome of acute promyelocytic leukemia (APL) is complex and consists disseminated intravascular coagulation (DIC) hyperfibrinolysis. Elastase, derived from malignant promyelocytes, believed to mediate the fibrinogeno- fibrinolysis by aspecific proteolysis. In this study we measured role elastase in fifteen patients with APL using an assay for degraded fibrin(ogen) results were compared those obtained sepsis induced DIC. High levels observed APL. fibrinogen fibrin degradation...

Upon stimulation, polymorphonuclear leucocytes (PMNs) release potent serine proteases, i.e. elastase, cathepsin G and proteinase 3, which contribute to the degradation of tissue plasma components. Here, we describe development a test assess PMN-mediated fibrinogenolysis as biochemical marker for actual PMN-derived proteolysis in vivo, useful monitoring therapeutic efficacy, elastase inhibitors. We generated monoclonal antibody (MAb), designated 1-1/B3, with high affinity elastase-degraded...

Summary Fibrin formation is a multistep process initiated by thrombin. At first thrombin converts fibrinogen to fibrin molecules which in vivo form soluble complexes with fibrinogen. Soluble considered be an early biochemical marker for intravascular and impending thrombotic events, such as deep venous thrombosis (DVT), pulmonary embolism (PE) disseminated coagulopathy (DIC). A new enzyme immunoassay (EIA) was developed on the basis of monoclonal antibody directed against specific...

We recently described new pathogenic variants in VRK1, patients affected with distal Hereditary Motor Neuropathy associated upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Neurons (hiPSC-MN) from these display Cajal Bodies (CBs) disassembly and defects neurite outgrowth branching. here focused on the Axonal Initial Segment (AIS) related firing properties of hiPSC-MNs patients. found patient's Action Potential (AP) was smaller amplitude, larger duration,...

Elastase, released by stimulated polymorphonuclear leukocytes (PMN), is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) especially emphysema. A test that can detect release elastase activity from PMN would be valuable monitor therapy or identify patients at risk. The authors aimed isolate and characterize monoclonal antibodies (mAb) with a high affinity for neo-antigenic determinant high-molecular weight degradation product fibrinogen...